M4I

Infrastructure and User Services 

M4I has an unique infrastructure that enables state-of-the-art molecular of complex surfaces to unravel molecular structure and composition using different imaging modalities. A distinctive mass suite of mass spectrometry based imaging systems is combined with state of the art spatial transcriptomics, cryo-electron microscopy and high end optical microscopy, all available to our user base. Complementary molecular imaging instruments allow the determination of the spatial distribution of intact, biomolecules from cellular and tissue surfaces with spatial resolutions ranging from 200 nm to 200 micrometer through a combination of targeted and untargeted strategies. Various “SpatialOMX” technologies are used to investigate the structure-function relation of biomolecules in their tissue environment using MS image guided laser capture microdissection combined with liquid chromatography MS based lipidomics, metabolomics, glycomics and proteomics. M4i’s advanced cryo-transmission electron microscopy (Cryo-TEM) instrumentation enables high-resolution 3D reconstruction through single-particle analysis as well as cryo-electron tomography of thicker cellular samples. Additionally, M4i has recently invested in an innovative system capable of imaging macromolecular assemblies that utilizes parallel detection capabilities of a Timepix3 detector. The infrastructure is equipped with several HPLC systems, as well as robots, image processing and analysis tools, including tissue classification and correlation software and protein data basing tools and a large scale data storage and cluster computing facility. The facility is equipped with a sample handling and preparation tools for EM and MS that enable controlled and reproducible protocols. These includes devices for cryosectioning, staining, graphene liquid cells, analytical microscopy, matrix deposition and surface coating.   

Examples/description of the type of research 

M4i facilitates interdisciplinary spatial biology, complex surface analysis, instrumentation development and clinical translation in various research domains. User research in molecular imaging and spatial biology targets key challenges in the contextual analysis of (single) molecules in life sciences, materials sciences and innovative chemistry. Electron microscopy (EM) visualizes the atomic structures of cellular building blocks, mass spectrometry (MS) and omics techniques map molecular signals at the (sub)cellular level, spatial transcriptomics visualizes RNA activity and light microscopy shows the dynamics and development of living systems. Imaging mass spectrometry can map the molecular metabolism of a single cell in the context of biological tissue, while nanoscopy distinguishes individual molecules in the context of a cell.  

M4i’s research studies local molecular mechanisms in single cells in their native tissue context to drive personalized medicine. MS based molecular pathology rapidly identifies and classifies single cells in organoids and tissue sections, used to evaluate the molecular heterogeneity of tumor tissue microenvironment. This information on molecular complexity is a key element in studies relevant for immune response and infiltration, regenerative medicine, therapy response needed for personalized medicine. The research facilitated across the breadth of the LSH community aid in improved diagnostics, and is essential for innovations in biomaterials and drug research. The molecular imaging infrastructure of M4i is used to trace new drugs and their metabolites in pharmaceutical DMPK (Drug metabolism and pharmacokinetics) imaging research as well as toxicological studies at cellular levels. Clinical imaging research currently focuses on immunology, infectious diseases, oncology and neurodegenerative diseases. 

How to access the infrastructure? 

Access to the infrastructure is provided through M4i’s website, Eurobioimaging and NEMI. M4i offers predominantly physical access to the infrastructure as part of our Collaborative Open Research Education (CORE) philosophy. The complexity of the imaging & omics experiments requires substantial user training on site. Users are provided with remote access to instruments and data when needed with support of in house technical staff. Data processing tools are made available virtually. Trained users can be provided with remote access to certain systems for remote monitoring and control of experiments.